We have overexpressed the HIV-1 tat and the HTLV-I tax proteins using an eucaryotic baculovirus-insect cell system. In analyzing the molecular mechanism(s) of tat and tax, we have noted the following salient observations: 1) neither tat or tax appears to function through direct binding to its respective target sequence in the viral LTR; 2) activation of the respective LTRs by the HIV-1 tat or the HTLV-1 tax proteins occurs in the absence of de novo cellular protein synthesis; 3) tax activates the HTLV-1 LTR through a set of triply-repeated 21 bp sequences which contain a consensus cAMP-responsive motif; and 4) a number of host cell proteins specifically bind to the HIV-1 TAR RNA sequence element. Our current working hypothesis is that activation of the HIV-1/HTLV-1 LTR is mediated through functional interactions between preexisting cellular transcription factors and the viral trans-activator proteins.